Biogerontology最新文献

Dermal fibroblasts are pivotal in maintaining skin integrity through extracellular matrix (ECM) production, a process compromised during aging due to oxidative stress from excessive reactive oxygen species (ROS). Salvia miltiorrhiza Bunge (Danshen, DS), a medicinal plant rich in bioactive compound-rich dried roots, has demonstrated broad therapeutic potential. This study investigates the anti-aging properties of Danshen callus (DSC)-an undifferentiated cell mass derived from leaf tissue culture, as a sustainable and controlled source of bioactive compounds. Using hydrogen peroxide (H₂O₂)-induced premature aging and chronological aging models in human dermal fibroblasts (HDFs), we evaluated DSC effects on redox homeostasis and senescence. Pretreatment and posttreatment with DSC significantly enhanced HDF viability, restored ECM synthesis, suppressed MMP-1 secretion, and reduced senescence-associated markers in H₂O₂-induced premature aging HDFs. Mechanistically, DSC activated the Nrf2/ARE pathway, mitigating ROS accumulation and reinforcing antioxidant defenses. Crucially, comparative analysis revealed DSC superior efficacy over native Danshen (DS) in both aging paradigms. These findings highlight DSC potential as a novel, plant-based therapeutic agent for anti-aging cosmetic formulations, leveraging agricultural waste for sustainable skincare solutions.

Ovarian aging, recognized as one of the initial signs of systemic aging, is marked by a progressive reduction in both the number and quality of oocytes, which has a profound effect on female fertility. In spite of the advancements in assisted reproductive technologies, these methods fail to tackle the fundamental molecular mechanisms that drive ovarian senescence. Recent surveys have underscored the significant role of epitranscriptomic regulation, especially the N6-methyladenosine (m6A) modification, in regulating RNA stability, translation, and cellular functionality. Fat mass and obesity-associated (FTO), a m6A demethylase, has been identified as a crucial regulator of granulosa cell homeostasis, influencing pathways related to oxidative stress, mitochondrial integrity, apoptosis, and cellular senescence. A decrease in FTO expression in aging ovaries is associated with increased m6A levels, destabilization of heterochromatin, dysregulation of transposable elements, and the upregulation of senescence-associated genes such as FOS. Moreover, regulation of genes such as MFN2, MMP2, and P53 by FTO has been shown to sustain mitochondrial function, uphold ERK signaling, and prevent apoptosis in granulosa cells. In summary, these discoveries position FTO as a pivotal element in the molecular framework governing ovarian aging, presenting promising opportunities for therapeutic strategies aimed at preserving female reproductive capacity.

Chemokines are small molecule secreted proteins that regulate biological processes such as chemotaxis, hematopoiesis, and angiogenesis, typically functioning through binding to G-protein-coupled receptors (GPCRs) on the cell surface. The chemokine family can be classified into four major types based on the differences in their conserved cysteine motifs at the N-terminal: CC, CXC, CX3C, and XC. Among them, the CXC family occupies a central position in the chemokine group. Due to their vital role in biological processes, chemokines have become a key focus of research in various complex diseases. Cell senescence is linked to various factors, including DNA damage and telomere shortening, marked by cell cycle arrest. Senescent cells impact both local and systemic microenvironments via the senescence-associated secretory phenotype (SASP), and CXC chemokines, as critical components of SASP, have been demonstrated to play important roles in various age-related diseases and cancers. However, the role of chemokines, especially CXC chemokines, in cellular senescence and the diseases they mediate has not been fully elucidated. This review summarizes the mechanism of action of CXC chemokines, the latest progress in their role in cellular senescence and related diseases, and discusses the potential of CXC chemokines as biomarkers and therapeutic targets.

Although most research on testicular aging has traditionally centered on germ cells, recent transcriptomic evidence shows that Sertoli cells are actually the most sensitive cell type to aging, displaying the highest number of aging-related differentially expressed genes and the greatest increase in transcriptional noise. As age advances, Sertoli cells undergo progressive quantitative loss, aberrant morphology, and disorganization of cytoskeletal and junctional structures, changes that collectively impair their ability to maintain the seminiferous epithelium and support germ cell development. This review therefore focuses on the key molecular processes underlying Sertoli cell aging, particularly the accumulation of cellular damage-including oxidative, mitochondrial, metabolic, and DNA lesions-and epigenetic alterations, such as dysregulated histone methylation and chromatin remodeling. Through addressing whether Sertoli cells predominantly undergo apoptosis, necrotic-like degeneration, or persist in a dysfunctional, senescence-associated state, this review highlights how their altered fate contributes to age-related male reproductive decline.

Fat plays a key role in maintaining energy balance and supporting various physiological processes. HuAge-related disorders in fat utilization are increasingly prevalent, contributing to impaired energy balance, heightened metabolic disease risk, and increased cardiovascular dysfunction. The mechanism of age-induced disorders of fat utilization remains unclear. This study aims to explore the key factor affecting fat digestion and absorption during aging. Mice of different ages were used to analyze the changes of physiological and metabolic parameters with aging, including metabolic rate, energy expenditure, lean mass and apparent digestibility. Results showed that respiratory energy metabolism declined and fat apparent digestibility decreased significantly by more than 4% with aging. Fat is initially hydrolyzed in the intestine through combined actions of digestive enzymes and bile acids. Thus, the pancreatic lipase activity and total bile acids content were measured. The results revealed no significant changes in these factors. Furthermore, factors affecting fat absorption including intestinal structure and transporters expression were assessed. It was found that the crypt depth and villi height did not change significantly with age. Notably, intestinal proteomics analysis indicated that the expression of fatty acid transporter protein 4 (FATP4) was reduced by more than 50% in aged mice. In conclusion, this study demonstrated that age-related decline in FATP4 expression is linked to impaired intestinal fat absorption. This association may underlie the decreased fat apparent digestibility and impaired fat utilization during aging. These findings reveal the intrinsic mechanisms of age-induced dysregulation of fat utilization and providing a theoretical basis for enhancing fat utilization in older adults.

Cereal grains contain bioactive compounds that may influence longevity. We investigated the effects of 20 cereal varieties on longevity and healthspan in Drosophila melanogaster, including triticale, bread wheat, durum wheats, ancient wheats, and regional varieties. Cereal-based diets exhibited sex-specific differences relative to cereal-free controls: females showed 3-13% longer lifespans while males exhibited reduced lifespans by up to 19%. In females, clear patterns were observed: pronounced lifespan differences (3-11% longer than controls) were concurrent with higher thermotolerance, while moderate lifespan differences (2-6% longer than controls) were associated with greater oxidative stress resistance and locomotor activity, but lower starvation resistance than controls. Males demonstrated higher stress resistance than controls despite shortened lifespan. Gene expression analysis revealed that female-specific lifespan differences were concurrent with elevated expression of immune-related genes (AttA, CecA1, DptA). These results suggest cereal-mediated longevity differences operate through sex-specific physiological pathways involving trade-offs between stress resistance and metabolic regulation.

Circulating tumor DNA (ctDNA), the tumor-originating fraction of cell-free DNA (cfDNA), is widely used as a biomarker for cancer detection and therapeutic monitoring; however, its direct biological impact on normal cells remains insufficiently understood. Since ctDNA contains tumor-derived molecular features, we hypothesized that it could serve as a signal that induces stress responses in healthy stromal cells. In this study, ctDNA and cfDNA were isolated from the conditioned media of B16-F10 melanoma and L929 fibroblast cultures, respectively, and applied to mouse embryonic fibroblasts (MEFs) at concentrations of 100 and 500 ng/mL for 24 h. Senescence was evaluated by SA-β-Gal staining alongside quantitative PCR analysis of senescence and SASP-associated genes, including p16, p21, p53, IL-6, and IL-1β. ctDNA treatment induced a pronounced, dose-dependent increase in senescence marker expression and SASP cytokine production, accompanied by elevated SA-β-Gal staining, whereas cfDNA treatment elicited no significant change compared to controls. These results indicate that ctDNA may act as a biologically active stimulus capable of eliciting senescence-like responses in normal fibroblasts, supporting the possibility that tumor-derived extracellular nucleic acids contribute to alterations in stromal behavior within the tumor microenvironment.

The increasing elderly population has brought healthy aging into focus. Aging is a multifactorial process characterized by the progressive decline of cellular and tissue functions, largely due to cumulative oxidative stress. Antioxidant-based strategies have therefore gained prominence as potential interventions. This study investigated the protective and therapeutic effects of Squalene (SQ) and Saponin (SP), individually and in combination, on aging-related biomarkers in brain tissue using a D-Galactose (D-Gal)-induced rat model. Forty-eight male Sprague-Dawley rats (200-250 g) were randomly divided into eight groups (n = 6). Aging was induced in four groups via intraperitoneal administration of D-Gal (300 mg/kg/day) for six weeks. One group received no antioxidants, while others were treated orally with SQ (2.66 mL/kg/day), SP (100 mg/kg/day), or their combination. Non-aging groups received the same antioxidant treatments without D-Gal. At the end of the intervention, brain tissues were collected for biochemical analysis. Spectrophotometric assessments included Malondialdehyde (MDA), Glutathione (GSH), Nitric oxide derivatives (NOx), Ascorbic acid (AA), and Protein carbonyls (PC). Forkhead Box O3A (FOXO3A), Nuclear factor erythroid 2-related factor 2 (NRF2), Sirtuin 1 (SIRT1), Paraoxonase 1 (PON1), and Klotho were quantified by ELISA. Combined SQ and SP treatment significantly decreased oxidative stress markers (MDA, NOx, PC) and increased antioxidant defenses (GSH, AA) as well as aging-related molecules (FOXO3A, NRF2, SIRT1, PON1, Klotho) (p < 0.05). Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels were also reduced. These findings demonstrate, for the first time, that combined SQ and SP administration can mitigate aging-related oxidative stress and molecular alterations in brain tissue.

Skeletal muscle aging is characterized by progressive functional decline and molecular remodeling, yet how different muscle types respond to aging remains incompletely understood. Here, we performed integrated transcriptomic and metabolomic profiling of three functionally distinct muscles-gastrocnemius (GA), soleus (SOL), and tibialis anterior (TA)-from young (3-month) and aged (24-month) C57BL/6J male mice. Our multi-omics approach revealed both shared and muscle-specific molecular signatures of aging. While all three muscles exhibited a core set of 83 commonly altered genes enriched in circadian rhythm, xenobiotic metabolism, and immune signaling pathways, each muscle displayed unique aging trajectories. GA showed 881 differentially expressed genes with prominent alterations in PI3K-Akt and p53 signaling; SOL exhibited 1232 changes emphasizing oxidative phosphorylation and inflammatory responses; TA demonstrated the most extensive remodeling with 1492 altered genes, particularly in extracellular matrix organization and fatty acid metabolism. Metabolomic analysis revealed muscle-specific metabolic reprogramming: GA showed disrupted pentose phosphate and arginine pathways; SOL exhibited altered branched-chain amino acid metabolism; TA displayed TCA cycle perturbations. Notably, the coordination between transcriptomic and metabolomic changes varied by muscle type-GA showed decoupled responses, while SOL and TA demonstrated compensatory inverse relationships. Lipid metabolism emerged as a critical aging-associated process with distinct muscle-specific adaptations: SOL upregulated antioxidant defenses, TA activated compensatory PPAR and PI3K-Akt signaling, while GA showed intermediate responses. Furthermore, receptor-ligand correlation analysis revealed age-dependent reorganization of intermuscular communication networks, with enhanced chemokine signaling and altered growth factor crosstalk. These findings establish that skeletal muscle aging involves both systemic responses and highly muscle-specific molecular adaptations, providing insights for targeted therapeutic strategies against sarcopenia.